Triphenylphosphine → 1-[2-Fluoro-4'-(4-trifluoromethyl-cyclohexyloxy)-biphenyl-4-yl]-cyclopropanecarboxylic acid

HRID 492281

Reaction equation

HRID 492281 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[F:13][C:14]1[CH:19]=[C:18]([C:20]2([C:23]([OH:25])=[O:24])[CH2:22][CH2:21]2)[CH:17]=[CH:16][C:15]=1[C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:52][C:53]([F:62])([F:61])[CH:54]1[CH2:59][CH2:58][CH:57](O)[CH2:56][CH2:55]1>C1COCC1>[F:13][C:14]1[CH:19]=[C:18]([C:20]2([C:23]([OH:25])=[O:24])[CH2:22][CH2:21]2)[CH:17]=[CH:16][C:15]=1[C:26]1[CH:27]=[CH:28][C:29]([O:32][CH:57]2[CH2:58][CH2:59][CH:54]([C:53]([F:62])([F:61])[F:52])[CH2:55][CH2:56]2)=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 27797654-(Trifluoromethyl)cyclohexan-1-olHCID 116014911-(2-Fluoro-4'-hydroxy-biphenyl-4-yl)-cyclopropanecarboxylic acid

Product 1

HCID 103649281-[2-Fluoro-4'-(4-trifluoromethyl-cyclohexyloxy)-biphenyl-4-yl]-cyclopropanecarboxylic acidYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (370 μL, 2.4 mmoles) is added to a solution of 200 mg of 1-(2-fluoro-4′-hydroxy-biphenyl-4-yl)-cyclopropanecarboxylic acid (0.8 mmoles), triphenyl phosphine (623 mg, 2.4 mmoles) and 4-trifluoromethyl cyclohexanol (400 mg, 2.4 mmoles) in dry THF (3 mL) at 0° C. under nitrogen atmosphere. The resulting clear orange solution is left under stirring overnight, then quenched with water and extracted with ethyl acetate. The organic phase is washed with 10% w/v HCl solution, dried on Na2SO4 and evaporated. Purification by chromatography on silica gel by eluting with methylene chloride:methanol 98:2 v/v furnishes 1-[2-fluoro-4′-(4-trifluoromethyl-cyclohexyloxy)-biphenyl-4-yl]-cyclopropanecarboxylic acid as a white solid.

Workup

  1. waitThe resulting clear orange solution is left
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. washThe organic phase is washed with 10% w/v HCl solution
  5. customdried on Na2SO4
  6. customevaporated
  7. customPurification by chromatography on silica gel
  8. washby eluting with methylene chloride:methanol 98:2 v/v

Sources & evidence

ORD record
ord-8f1de401090f455eba66dab1ea6cef4f
Source dataset
uspto-grants-2009_05
Patent number
US07531692B2

Linked notes

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